This application from the Group Health (GH)/University of Washington (UW) eMERGE team proposes specific aims designed to advance integration of genomic data into clinical practice with a focus on clinical discovery and implementation on Mendelian forms of colorectal cancer and/or polyposis (CRC/P) and incidental findings in other actionable genes. Our aims will also allow us to address challenges involved in bringing genomic medicine into standard medical care. Our focus on CRC/P, and quantitative traits and incidental findings (IF) in other actionable genes represents a unique opportunity to move the field forward towards the goal of bringing genomic medicine into effective, standard medical practice in an everyday community practice setting. We have 3 Aims. Aim 1: Genomic medicine discovery and implementation focused on CRC/P, Triglycerides (TG), and neutrophil count (NPC). We proposed sequencing of 1000 CRC and 1000 Asian ancestry participants, to achieve sub- aims of understanding the genetic basis of CRC, TG, and NPC. Aim 2: Integrate genomic information into GH-wide clinical care and the EMR. We will develop intuitive, comprehensive reports to return CRC and other genes deemed actionable by the American College of Medical Genetics and Genomics (ACMG). We will incorporate stakeholder input and then to implement integrated processes and tools into an integrated delivery system with a focus on CRC/P and Long QT syndrome. We will develop and evaluate educational outreach and online resources. Aim 3: Evaluate the effectiveness and economic impact of result return to patients and their families. We will implement a novel tool to increase family communication of CRC genetic results and evaluate the economic impact and cost effectiveness of this tool as well as of returning IFs. Completion of the work in this eMERGE III proposal will guarantee that the Seattle site remains an engaged and effective leader in the eMERGE network in support of NHGRI's mission to ensure that barriers to successful integration of genomic medicine in clinical care are overcome.